tbuckley/cabot-search huggingface dataset:
Associations between micro-geographic social vulnerability and disparities in cancer incidence.
Authors: Ismail Aijazuddin, Abdurahman Alloghbi, Ammar Sukari
Journal: Journal of Clinical Oncology (2023)

e18523 Background: Disparities in cancer incidence and diagnosis are the result of complex physical-social-environmental interactions. Geography is one crucial lens for assessment of these disparities. The CDC’s Social Vulnerability Index (SVI) ranks micro-geographies such as Census Tracts based on social factors and can be used to identify health disparities in measures such as cancer incidence. Methods: Actual and age-adjusted expected incidence of common cancers were obtained from the New York State Cancer Registry for 2013-2017 at the Census Tract level. Data were merged with the CDC’s Overall SVI rating for 2016 at the Census Tract level. Analysis included 4,647 Census Tracts, accounting for 97.71% of New York State’s 2016 population (19,078,306 population included). For each cancer, actual and expected incidence were grouped by overall SVI percentile, then percentage deviation from expected cancer incidence was calculated. Pearson correlational test and two-tailed t-test were performed for incidence deviation of each cancer by overall SVI percentile. Results: In New York State, significant correlations between Census Tract Overall Social Vulnerability Index (SVI) percentile and percentage deviation from expected cancer incidence were found for 5 out of 6 cancers reported in the State Cancer Registry. Strong positive relationships between degree of vulnerability and deviation from expected incidence were found for Lung Cancer (R = 0.75, p &lt; 0.001) and Colorectal Cancer (R = 0.67, p &lt; 0.001). Strong negative relationships were found for Female Breast Cancer (R = -0.90, p &lt; 0.001), Urinary Bladder Cancer (R = -0.76, p &lt; 0.001), and Non-Hodgkin Lymphoma (R = -0.73, p &lt; 0.001). A significant correlation was not found for Prostate Cancer, which demonstrated a bimodal relationship with higher excess incidence at low and high vulnerability ratings. Conclusions: There are statistically significant increases in reported incidence of Colorectal and Lung Cancers in more vulnerable Census Tracts in NY State. Paradoxically, there are significant decreases in reported incidence of Breast Cancer, Bladder Cancer, and Non-Hodgkin Lymphoma in more vulnerable Census Tracts. Further exploration of micro-geographic trends is critical to understand the extent to which these disparities are explained by true differences in cancer incidence or by variations in screening access and utilization. [Table: see text]
Epcoritamab + R<sup>2 </sup>regimen and responses in high-risk follicular lymphoma, regardless of POD24 status.
Authors: Reid Merryman, David Belada, Anna Sureda, Sirpa Leppä, Joost S.P. Vermaat, Harald Holte, Martin Hutchings, Pieternella Lugtenburg, Sven de Vos, Pau Abrisqueta, Marcel Nijland, Jacob Haaber Christensen, Björn E. Wahlin, Kim M. Linton, Liwei Wang, Aqeel Abbas, Ali Rana, Syed Quadri, Lorenzo Falchi
Journal: Journal of Clinical Oncology (2023)

7506 Background: Follicular lymphoma (FL) is a heterogeneous disease. Early progression after initial treatment (tx) with chemoimmunotherapy (CIT), POD24, occurs in around 20% of patients (pts) and strongly predicts poor outcomes. There is no standard tx approach for high-risk, relapsed or refractory (R/R) FL (high-risk subgroups in Table). Novel options are needed to improve efficacy in pts with high unmet need. Epcoritamab, a subcutaneous (SC) T-cell–engaging bispecific antibody, demonstrated impressive single-agent antitumor activity and a manageable safety profile in R/R FL (Hutchings et al, Lancet 2021) and shows promise combined with standards of care. Here we present pooled analyses from cohorts 2a and 2b of the ongoing phase 1/2 EPCORE NHL-2 trial (NCT04663347) of epcoritamab with rituximab + lenalidomide (R 2 ). Methods: Pts with R/R CD20 + FL received epcoritamab SC + R 2 for 12 cycles (Cs; 28 d each). Epcoritamab was dosed QW in C1–3, Q2W in C4–9, and Q4W in C≥10 (2a) or QW in C1–2 and Q4W in C≥3 (2b) for ≤2 y. Results: As of Oct 31, 2022, 109 R/R FL pts had received epcoritamab 48 mg + R 2 in 2a and 2b. Median age was 65 y, 56% of pts had FLIPI 3–5, 61% had stage IV disease, and 59% had only 1 prior tx. Most had received alkylating agents (92%) or anthracyclines (62%); 2 had prior CAR T. At a median follow-up of 8.8 mo (range, 1.2–18.5), 82% were still on tx. The most common tx-emergent AEs were: CRS and neutropenia, 48% each; injection-site reactions, 38%; and fatigue, 33%. CRS events were mostly low grade (G; 46% G1–2, 2% G3) and mostly occurred following the first full dose on C1D15; all resolved and none led to discontinuation. ICANS occurred in 2 pts (G1, G2) and resolved. In 101 efficacy-evaluable pts, overall response rate (ORR) was 97%, with complete metabolic response (CMR) in 86%. Notably, pts achieved higher ORR/CMR rates with epcoritamab + R 2 vs their immediate prior tx line (ORR, 97% vs 85%; CMR, 86% vs 60%). Estimated 6-mo progression-free survival was 93%. In second-line (2L) pts with POD24, ORR/CMR rates were 95%/90% (additional high-risk subgroup data in Table). Additional data with longer follow-up will be presented. Conclusions: Epcoritamab + R 2 showed potent antitumor activity and a manageable safety profile in a large R/R FL population. Encouraging responses were seen in pts with high-risk disease, suggesting epcoritamab SC may abrogate negative effects of high-risk features. A separate POD24 cohort is planned, and epcoritamab + R 2 is being studied in the phase 3 EPCORE FL-1 trial (NCT05409066). Clinical trial information: NCT04663347 . [Table: see text]
Impact of risk-reducing mastectomy on quality of life of women with Li-Fraumeni syndrome.
Authors: Natalia Polidorio, Renata Lazari Sandoval, Pâmela Bioni, Maria Isabel Waddington Achatz
Journal: Journal of Clinical Oncology (2023)

10623 Background: Risk-reducing mastectomy (RRM) is a common strategy for managing breast cancer (BC) risk in women with Li-Fraumeni syndrome (LFS). Data on uptake and health-related quality of life (HRQoL) in LFS are limited and often extrapolated from BRCA scenario, despite the lack of evidence on survival benefits in LFS. This study evaluated RRM uptake and its impact on HRQoL in women with LFS. Methods: TP53 PV female carriers from a Brazilian LFS cohort from January 2012 to December 2022 were eligible. After informed consent, 90 women reported oncological status, uptake of RRM, and completed BREAST-Q questionnaire. Scores were compared among different BC risk management strategies and minimal important difference (MID) of ≥ 4 was described. Multivariable analyses were performed to identify surgical factors related to HRQoL outcomes. Results: 71.7% (n=33) of women diagnosed with unilateral BC (n=46) underwent contralateral risk-reducing mastectomy (CRRM) at a median age of 39 years. Among unaffected BC women (n=44), 36.3% underwent bilateral risk-reducing mastectomy (BRRM) at a median age of 36 years. CRRM was associated with lower scores for psychosocial (64[±19] vs 93[±21], p=.05) and physical well-being (72[±16] vs 92[±18], p=.001). BRRM women had lower physical well-being scores (72[±19] vs 92[±13], p=.003). MID associated with worst HRQoL outcomes were seen in all four domains on CRRM women and on satisfaction with breasts and physical well-being of BRRM patients (table). Nipple-sparing mastectomy (NSM) presented better psychosocial (74[±20] vs 52[±19], p=.04) and sexual well-being (60[±20] vs 46[±20], p=.05) when compared to skin-sparing mastectomy (SSM) on CRRM patients and with higher sexual well-being (60[±20] vs 46[±20], p=.05) on BRRM patients. Women with BRRM &gt; 2 years had better physical well-being (83[±14] vs 56 [±12], p&lt;.001). There were no significant differences in scores of women with age £35 years at the time of BRRM, although MID ≥ 4 was observed on psychosocial and sexual well-being and satisfaction with breasts: -23.0, -14.4, and -20.0, respectively. Conclusions: We observed high rates of RRM in LFS women and those were associated with worse outcomes on breast HRQoL in comparison to surveillance. The potential benefits and harms of RRM should be carefully discussed with patients before performing it, especially in LFS women where the survival benefits of these interventions remain uncertain. [Table: see text]
Outcomes of patients with primary refractory multiple myeloma in the era of triplet and quadruplet induction therapy.
Authors: Charalampos Charalampous, Utkarsh Goel, Prashant Kapoor, Moritz Binder, Francis Buadi, Joselle Cook, David Dingli, Angela Dispenzieri, Morie A. Gertz, Wilson I. Gonsalves, Suzanne R. Hayman, Miriam A. Hobbs, Yi Lisa Hwa, Taxiarchis Kourelis, Martha Lacy, Nelson Leung, Yi Lin, Rahma M. Warsame, S. Vincent Rajkumar, Shaji Kumar
Journal: Journal of Clinical Oncology (2023)

8051 Background: Patients with multiple myeloma (MM) that do not respond to initial therapy have worse outcomes compared to primary responders, and effective treatments are lacking in this population. However, the outcomes of primary refractory disease in the modern treatment era have not been studied. Methods: From 2007-2019, we reviewed MM patients treated with triplet/quadruplet therapy in our institution to assess the incidence of primary refractory disease and the impact of salvage therapies in this population. Primary refractory disease was defined as either progressive disease or stable disease at 4-6 cycles. The Kaplan-Meier estimates were used for survival probabilities. PFS and OS were calculated from MM diagnosis to progression, escalation/change of treatment, or death, respectively. For the primary refractory group, the second PFS and second OS were measured from the start of second-line therapy. The Cox regression model was used for multivariable analysis with the following variables (age, ISS, induction therapy, FISH, and bone marrow plasma cells at diagnosis). Results: We identified 1127 patients, of which 1086 were evaluated for hematologic response after 4-6 cycles. Of these, 93.3% (1013) had evidence of response, while 6.7% (73) had primary refractory disease. With a median OS of 50.7 months, patients with primary refractory disease had an increased risk for shorter survival in univariable and multivariable analysis (HR: 3.6, 95% CI = 2.61 – 4.96, HR = 3.89, 95% CI = 2.68 – 5.65, respectively). In subgroup analysis of primary refractory patients, the median second PFS and second OS from the first relapse were 11.9 months (95% CI: 8.7 – 17.3 months) and 43.4 (95% CI: 31.4– 75.9 months), respectively. Patients that received 2 nd line ASCT had increased second PFS (20.9 vs. 8.1 months, respectively, p &lt; 0.01) and second OS (74.7 vs. 31.3 months, respectively, p = 0.02) compared to patients that did not. Patients that took daratumumab as the second line did not have any significant survival differences compared to those who did not, p = NS. Conclusions: We conclude that early progression remains a significant factor for shorter OS in the current era, and salvage ASCT could be the most beneficial option for this population. [Table: see text]
A novel risk assessment metric for antimyeloma therapies and drug interactions.
Authors: Xuan Xu, Majid Jaberi-Douraki, Faiz Anwer, Beth Faiman, Louis Williams, Sandra Ann Mazzoni, Jack Khouri, Jason Neil Valent, Remya Ampadi Ramachandran, Jim Riviere, Nuwan Millagaha Gadara, Mobina Golmohammadi, Gerald Wyckoff, Christy Joy Samaras, Renato Verayo Samala, Shahzad Raza
Journal: Journal of Clinical Oncology (2023)

e24082 Background: New treatments for multiple myeloma (MM) improved both the clinical course and survival. These differ in their mode of action, safety profile, and adverse events (AEs). The goal of this study is to establish the benchmark for an integrated systematic investigation to assess the toxicity of different anti-MM drug regimens (AMDR). Methods: We curated 342,213 MM patient information from 2016–2022 from the FDA Adverse Event Reporting System. A total of 71 AMDR were evaluated in 7 different system organ classes when mapped to MedDRA. Drug-associated genes and AEs were also quantified as genetic evidence of a drug-AE combination. Gene-gene associations were then explored using the STRING database. We then developed a novel risk assessment metric that combined historical data from MM patients with drug-AE scores regarding the AE occurrence, the number of reported AE, and the genetic evidence of drug-gene and gene-AE associations (GAA). This likelihood-based rating metric includes (vH): (very) high MDR risk–(very) frequent AEs and mortality with (very) significant GAA evidence; and similarly computed for M: medium risk; and L: low risk. Results: Our risk assessment findings revealed single agents (carfilzomib (K), bortezomib (V), daratumumab (D), lenalidomide (R), melphalan (Mel), thalidomide (T), ixazomib (Ix), elotuzumab (El), isatuximab (Is) or dexamethasone (d)) illustrated very low profile of toxicity compared to combination regimens. Overall, we found that AMDR profiles showed higher toxicities in 4 different SyOCs (hepatobiliary, cardiac, nervous, renal) with nominal issues in 3 SyOCs (vascular, neoplasm, GI). AMDR toxicity significantly increased when d was added to the treatment compared to AMDR without d. Cardiac and vascular AEs were higher with K-based combinations. Hepatobiliary toxicities were higher with V, K, or T-based combinations. Secondary neoplasms were seen more frequently in patients who received high dose Mel followed by R. Conclusions: Our analysis of large data shows the association of SyOCs and graded toxicity profiles with unique AMDR. The single drug or doublets without dexamethasone seemed to show an improved AE profile compared to those with dexamethasone used as doublets, triplets, or quadruplets. Secondary cancer risk was much higher with high dose Mel followed by R compared with other AMDR. Our assessment system provides a framework for AMDR comparison toward future precision MM therapeutics based on unique drug doses, combination regimens, patient phenotypic risk profiles, secondary cancer surveillance and interplay of genetics and comorbidities. [Table: see text]
Results from a first-in-human phase I study of F182112, a B-cell maturation antigen (BCMA)-CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma.
Authors: Mingyuan Sun, Lugui Qiu, Yongqiang Wei, Jie Jin, Xin Li, Xue Liu, Shaohong Yin, Junyuan Qi
Journal: Journal of Clinical Oncology (2023)

8038 Background: F182112 is a BCMA x CD3 bispecific antibody that redirects CD3+ T cells to mediate T-cell activation and subsequent lysis of BCMA-expressing myeloma cells.NTP-F182112-001 is a First-in-human, Open-label, Multiple center Phase 1 Dose-Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetic, Immunogenicity, and Preliminary Efficacy of F182112 in Patients with Relapsed or Refractory Multiple Myeloma. Clinical trial information: NCT04984434. Methods: Eligible patients aged ≥ 18 years had received at least 2 prior multiple myeloma treatment regimens (not including autologous stem cell transplant) including a proteasome inhibitor, an immunomodulatory agent. Three dose cohorts (0.01, 0.1, and 0.3μg/kg) were planned for accelerated titration phase and the following dose cohorts (3, 10,20, and 30 μg/kg) were planed for the i3+3 dose escalation phase. F182112 were administered as QW or Q2W IV infusion. The primary endpoint was safety and tolerability assessed throughout the study by monitoring AEs per the CTCAE 5.0, except CRS per ASTCT 2018. Results: As of Feb 2,2023, 16 pts in the first 7 cohorts received F182112 (0.01-20 μg/kg). Median follow-up was 3.1 mo (range 0.9–11.7; median age 64 y [range 52–74]; 68% female). 9 (56%) pts had received ≥4 prior lines of therapy and 12 (75%) pts were refractory to last lines of therapy. The ORR was 43.8% (95% CI 19.8-70.1) among all enrolled patients (7/16). Of the 9 pts treated with ≥ 10 μg/kg F182112, 6 pts achieved a partial response (PR) or better (overall response rate; 66.7%), including 2 (22.2%) with a very good partial response or better.The most common treatment-related AEs were CRS (81%), lymphopenia (75%; grade 3/4: 69%), neutropenia (63%; grade 3/4: 44%), leukopenia (56%; grade 3/4: 50%), and anemia (31%). CRS and anemia events were all grade 1–2 and median duration time to CRS was 2 days (1-5). One dose-limiting toxicities (transient ALT elevation, grade 3) occurred at the dose group of 10 μg/kg. No pts required a F182112 dose reduction due to AEs. Conclusions: F182112 provides a novel immunotherapy approach for the treatment of Relapsed/ Refractory Multiple Myeloma that may yield improved clinical efficacy in heavily pretreated pts. Clinical trial information: NCT04984434.
Outcomes of childhood, adolescent, and young adult cancer survivors (CAYACS) with solid organ transplants: A population-based study.
Authors: Sumit Gupta, Cindy Lau, Vicky Ng, Mar Miserachs, Chia Wei Teoh, Melinda Solomon, Paul C. Nathan
Journal: Journal of Clinical Oncology (2023)

10056 Background: Organ toxicity requiring solid organ transplant (SOT) is a rare but serious effect of cancer treatment. Given restricted donor organ supply, teams must assess CAYACS requiring SOT in relation to potential recipients with non-malignant indications; decisions are limited by scant long-term outcome data. We compared long-term outcomes for CAYACS requiring SOT with other SOT recipients. Methods: All Ontario, Canada children &lt; 18 years at cancer diagnosed 1986-2021 at pediatric centres, and AYA aged 15-21 diagnosed at adult centres for acute leukemia, lymphoma, sarcoma, or testicular cancer between 1992-2012 were identified using population-based clinical databases. Patients with SOT prior to their primary cancer diagnosis were excluded. SOT was identified through linkage to healthcare databases; patients were matched 1:2 to non-malignant SOT recipients by sex, SOT year and type, and birth year. Post-SOT outcomes including overall survival (OS) and post SOT cancers were compared between CAYACS and SOT controls. Results: Among 16,533 CAYA with cancer, 85 received SOT: 46 liver, 18 kidney, 11 lung, and 10 heart. Among liver recipients, 33 (71.7%) were for primary cancer treatment (e.g. hepatoblastoma) vs. 13 (28.3%) for organ toxicity. Median age at original cancer diagnosis was 4 years [interquartile range (IQR) 1-13] and at SOT was 13 (IQR 3-20). CAYACS with SOT as treatment for long-term toxicity (liver subset plus all renal, lung, heart, N = 52) had a median time from cancer diagnosis to SOT of 9 years (IQR 4-16) and experienced lower 10-year OS from time of SOT [67.7%, 95 th confidence interval (95CI) 50.8-79.9] vs. SOT matched controls [86.0% (74.8-92.5); hazard ratio (HR) 3.9; 95CI 1.6-9.7; p = 0.003]. When stratified by SOT type, similar trends were seen but were only statistically significant among lung SOT recipients (Table). The 5-year cumulative incidence of primary cancer relapse from time of SOT among those who received liver SOT for primary cancer therapy was 15.9% (95CI 5.6-30.8). Among CAYACS who require SOT following organ toxicity, 10-year cumulative incidence of second cancers was 8.6%±4.2%; this was similar to the incidence of first cancer among SOT controls (6.4%±2.6%; HR 1.6, 95CI 0.6-4.0; p = 0.34). Conclusions: Though CAYACS requiring SOT have inferior survival compared to other SOT patients, the majority achieve long-term cancer-free survival. These data can inform discussions on the suitability of CAYACS for SOT. [Table: see text]
Perceived mental and physical health in patients with common cancers: A study using the PROMIS framework in All of Us database.
Authors: Rajaa Mohamed Salih, Yong Eun, Rahman Adesoji Olusoji, Noah Osei, Meena Ahluwalia
Journal: Journal of Clinical Oncology (2023)

10619 Background: The self-perception of one's mental and physical health (MH and PH) is of utmost importance for individuals diagnosed with cancer. This study focuses on the assessment of self-perceived mental and physical health (MH and PH) in individuals diagnosed with cancer. The Patient-Reported Outcomes Measurement Information System (PROMIS) framework is used to measure health outcomes, with PROMIS-PH measuring physical well-being and PROMIS-MH measuring mental health status. The study aims to evaluate self-reported mental and physical health of individuals with common cancers in the All of Us database, which includes over 414,000 participants in the US who have completed PROMIS-PH and PROMIS-MH surveys. Methods: We included participants from All of Us dataset version 6, which includes survey data collected between May 6, 2018 and January 1, 2022 who had available electronic health records data (N = 258,188). From the survey data, we calculated PROMIS-PH and PROMIS-MH score in participants with diagnosis code (ICD9/ICD10) of any cancers (N = 36377), breast (N = 5172), prostate (N = 5234), colon (N = 2366), and lung cancer (N = 2338). The study compared scores each cancer groups using Wilcoxon rank sum test, with a significance level of P &lt; 0.05. Analysis was performed in the web-based platform Jupyter Notebook using programming language R. Results: The study calculated PROMIS-MH and PROMIS-PH scores based on two questions, with response options valued from 1 to 5. The higher the score, the higher the level of perceived mental and physical health. Results showed that the mean PROMIS-MH score for all cancers was 7.38, with the highest score of 7.67 in prostate cancer and the lowest score of 7.10 in lung cancer. The mean PROMIS-PH score for all cancers was 7.31, with the highest score of 7.62 in prostate cancer and the lowest score of 6.71 in lung cancer. Prostate cancer group showed the highest PROMIS-PH and PROMIS-MH scores among the four cancer groups (P &lt; 0.05), while participants with lung cancer reported the lowest PROMIS-PH and PROMIS-MH scores (P &lt; 0.05). Additionally, breast cancer had higher PROMIS-MH and PROMIS-PH scores compared to all cancers (P &lt; 0.05), while lung cancer had lower PROMIS-MH and PROMIS-PH scores (P &lt; 0.05). There was no significant difference in PROMIS-MH score between all cancers and colon cancer. Conclusions: These results suggest that individuals with lung cancer may have a lower level of perceived mental and physical health compared to those with other cancers. Further research is needed to understand the underlying causes of these differences and to evaluate the effectiveness of interventions aimed at improving the well-being of individuals with cancer.